The Future of Medical Isotope Production and Use

Darrell R. Fisher, Ph.D.Isotope Sciences Program

March 18, 2011PNNL-SA-78497

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Our objective: Improve the supply of radioisotopes and develop exciting, new medical and industrial applications

Our isotope world

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• All matter consists of elements (atoms and molecules)

• 112 (or more?) elements

• Each element comprises several isotopes

• About 1600 isotopes

• Either stable or unstable (radioactive)

Hydrogen: 1H (99.985%, stable), 2H (0.015%, stable), 3H (trace, radioactive)

Carbon: 8C, 9C, 10C, 11C, 12C (98.9%, stable), 13C (1.1%, stable), 14C, 15C, 16C, 17C, 18C, 19C, 20C

T1/2 14C = 5715 years T1/2 11C = 20.3 minutes

Emits a beta(-) particle Emits a beta(+) particle, gammas

“Equipped with his five senses, man explores the universe around him and calls the adventure science.”

-- Edwin Powell Hubble, The Natureof Science, 1954

George Charles de Hevesy (1885 – 1966), Hungarian radiochemist; Nobel laureate (1943) for development and use of radiotracers in the study of chemical processes and metabolism

Of Sunday dinner and recycled pot roast, Manchester, (1911)

Ernest O. Lawrence (1901-1958), Nobel laureate in physics (1939) for work on the cyclotron and isotope production

University of California Radiation Laboratory, circa 1936

Building the 60-inch Berkeley cyclotron in 1937 with its 220-ton magnet

sodium-24, phosphorus-32, iodine-131

Dr. Joseph Hamilton (1907–1957), University of California at San Francisco

• worked closely with John and Ernest Lawrence and Glenn Seaborg on medical applications of newly discovered isotopes.

• helped transform the isotope sciences into a new field: nuclear medicine

Early thyroid rectilinear scan using iodine-131 (1954)

Radiolabeled antibodies: created new interest in yttrium-90

cancer cell

antigen binding site

antibody linker molecule

radioisotope

chelate

Yttrium-90 production at PNNL (1990-1999)

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The dark ages (1999-2003)

• Total loss of funding and mission responsibility• Loss of key staff• Struggle to keep the Fast Flux Test Facility

viable as a production source for medical isotopes

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The Renaissance (2003-2009)• New program strategy focused on technical

support to the private sector→ IsoRay Medical, cesium-131 seeds→ AlphaMed, Inc.→ Advanced Medical Isotope Corporation

• New program support from the Department of Energy in isotope production

• New purpose and mission• Collaboration with other national laboratories• New staff

Today: Enabling science, medicine, and industry

The Isotope Sciences Program at PNNL:represents a national technology resource

Our signature capability: high-purity radiochemical separations

Reid Peterson

Nicole Green

Our greatest asset: people

Brian Rapko

Amanda Johnsen

Chuck Soderquist

Jim Toth

Larry Greenwood

Mike Urie

Gregg LumettaGarrett Brown David BlanchardBrian Rapko Clark Carlson

Matt O’Hara

• DOE hazard category 2 facility for work with micrograms to kilograms of fissionable and non-fissionable radioactive materials

• 144,092 ft2 building with 40,000 ft2 of laboratory and more than 8,500 ft2 of hot cell space

• Extensive wet laboratories, shielded glove boxes, wet radiochemistry fume hoods, and a modern analytical laboratory

• 16 hot cells (4 new)

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Facilities: Radiochemical Processing Lab

Isotope production and distribution

Strontium-90 production as source for yttrium-90 Radium-224 generators for 212Pb/212Bi Gadolinium-153 in collaboration with Idaho National

Laboratory Radium-223 and thorium-227 production from legacy

actinium-227 (neutron sources) Radium-226 beneficial re-use for producing short-lived

alpha emitters (225Ac/213Bi) Neptunium-237 distribution Cesium-137 recycle for beneficial

re-use

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Focus on alpha-emitting radionuclides

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• Greatest cell-kill efficiency• Normal-tissue sparing• Ideal for treating

metastatic cancer

Melanoma to complete remission using targeted alpha therapy

Radiopharmaceutical and medical device design

Radionuclide polymer composites for direct intra-tumoralinjection

New, fast-resorbable seed design for controlled delivery of yttrium-90 microspheres

Apoferritin nanoparticle-biotin-streptavidin-antibody

227Thorium 5α 18.7d 89Zirconium β+ 3.3 d

Non-toxic, biodegradable construct Secure binding of radiometals and decay products Insoluble, non-toxic 8-nm nanoparticle contains multiple

radiometal atoms for high-dose radiation therapy

• Localized alpha radiation for effective cancer cell killing• High-resolution PET imaging

Where’s the nuclear reactor?

Although we do not have an operating nuclear reactor or a charged-particle accelerator as on-site isotope-production tools, we nonetheless: partner with other facilities and organizations with nuclear reactors and charged-particle acceleratorsprepare and ship radioisotopes extracted from long-lived (legacy) radioactive materials

Compact systems

“Next-generation” approach to isotope production where full-scale nuclear reactors and cyclotrons are too expensive or too complex to acquire and operateFully dedicated, right-sized, “on/off” systems

Proton accelerators Alpha accelerators Neutron generators Electron beam x-ray irradiation systems Stable-isotope plasma-separation systems

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Compact systems: proton accelerator

• First U.S. “compact” 7-MeV proton linear accelerator for medical isotope production (2008)

• Up and running, producing 18F for local hospitals

Advanced Medical Isotope Corporation, Kennewick

Next: compact alpha-particle linear accelerator

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• Advanced 30 MeV, 1.5 mA, high-efficiency, pulsed or continuous, plasma radiofrequency quadrupole drift tube

• Also accelerates protons, deuterons, 3He,12C• Lowest cost, highest output of key isotopes identified as

critical need: 82Sr, 67Cu, 211At, 117mSn, 210Po, 123I, 125I • $12M Private/federal funding proposed (Alpha Source)• Target fabrication and processing at PNNL Proposed

location (new addition)

Applied Process Engineering Laboratory (APEL), Richland

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Dream lofty dreams, and as you dream, so you shall become.

Your vision is the promise of whatyou shall one day be.

-- James Allen